Synthesis and antitumor activity of isolongifoleno[7,8‐d]thiazolo[3,2‐a]pyrimidine derivatives via enhancing ROS level

Abstract

A series of novel isolongifoleno[7,8‐d]thiazolo[3,2‐a]pyrimidine derivatives (4a–4x) were synthesized from isolongifolanone according fragment‐based design strategy, and their anticancer activity against human aortic smooth muscle cells (HASMC), human breast cancer (MCF‐7) cells, human cervical cancer (HeLa) cells, and human liver cancer (HepG2) cells were investigated. Results of the anticancer activity illustrated that most of the compounds showed potent antitumor activity and compound 4i proved to be the most active derivative with IC50 values of 0.33 ± 0.24 (for MCF‐7 cells), 0.52 ± 0.13 (for HeLa cells), and 3.09 ± 0.11 μM (for HepG2 cells), respectively. Moreover, we assessed the effects of 4i on cell apoptosis, cell cycle distribution, mitochondrial membrane potential, and reactive oxygen species (ROS) generation. The results indicated that compound 4i altered mitochondrial membrane potential and produced ROS leading to cell apoptosis of MCF‐7 cells in a dose‐dependent manner, however, without affecting cell cycle progression. These findings suggested that 4i was an effective compound and provided a promising candidate for anticancer drugs.

Synthesis and biological evaluation of dehydroabietic acid-pyrimidine hybrids as antitumor agents

“…1,2 Traditional chemotherapy is still one of the most common methods used for cancer therapy. 3 However, the chemotherapeutic drugs usually cause cytotoxicity on normal proliferating tissues and display signicant toxic side effects and drug resistance. 4 Thus, there is a pressing need for novel and more potent antitumor agents with high selectivity for tumor cells and low toxicity to normal tissue.…”

Polyphenols fromPrunus mume: extraction, purification, and anticancer activity

“…ROS is a metabolic by-product of aerobic respiration, which helps maintain redox homeostasis in cells. 48 Thus, ROS can serve as a new standard for determining cytotoxicity because increased intracellular ROS will interfere with the oxidative environment of cells and induce cell death. We determined the effect of representative L 1 on cellular ROS level in HepG2 cancer cells by flow cytometry.…”

P129, a pyrazole ring-containing isolongifolanone-derivate: synthesis and investigation of anti-glioma action mechanism

“…Among them, pyrazole-based anticancer agents have been widely used in clinical treatment [ 12 ]. Hence, building a functional pyrazole ring-containing isolongifolanone derivative has high potential, and our group has been working on the development and biological activities of turpentine and its derivatives [ 10 , 13 , 14 ]. In this study, we synthesized P129 as a derivative of isolongifolanone and investigated its anti-glioma effects and the underlying mechanisms.…”